The availability of pure preparations of relaxin has always been quite limited due to the difficulty of isolating and purifying it, as well as to the scarcity of organs from which to extract it (Bryant Greenwood G. D., Endocrine Review, 3-62-1982). These limitations and the difficulties in preserving the biological activity of the hormone produced a progressive lack of interest until an almost complete oblivion of relaxin, and finally even the disbelief in relaxin existence.
The purification and sequentiation of relaxin and its production by genetic engineering, obtained from 1974 to 1983, offered new possibilities to finally research and understand the biology and the role of this hormone. In this respect see Sherwood et al., Arch. Biochem. Biophys. 160-185-1974; James et al., Nature 267, 554, 1974; Hudson et al., Nature, 301, 628, 1983; Bigazzi M. et al, Biology of Relaxin and its role in the human, International Congress Series 610, Excerpta Medica-Amsterdam-1993.
Actually, there is a bulk of evidence that RLX is a multifunctional hormone, efficacious on reproductive organs, mammary glands and connective tissues, but so far no clinical use has been realized.
A new possible target for RLX could be the cardiovascular system. The cardiovascular system can be divided into three different main sections:
the heart represents the pump of the system, PA1 the blood vessels represent the circulation pipes, PA1 the blood circulates in the vessels and contributes in a positive or negative way to circulation through the hemostatic system and through the concentration of various substances such as lipids, electrolytes, water and the like.
Some diseases or dysfunctions of the cardiovascular system can occur separately only in one of these main sections without affecting directly the others (such as the contractile failure and rhythm disturbances of the heart, some congenital abnormalities of the vessels or alterations in the hemostatic chain as thrombophilic or hemophilic diseases etc.).
Some of the more frequent circulatory diseases can begin in one section but involve soon also other parts of the system. This is the case of arteriosclerosis in which both the alterations of the blood composition and of the arterial walls are responsible for the pathogenesis and clinical features of the disease.
The circulatory disease which derives from arteriosclerotic processes represents one of the major problems of mankind. In fact it is the most frequent cause of death, at least in 4% of the population (especially from myocardial or cerebral infarction). This explains the great interest of researchers in this field.
Presently many different pharmacological tools are known and used to correct the thrombo-ischemic diseases of circulation, separately aimed at vessel dilation or blood clotting correction, clot dissolution, blood lipid reduction and so on.
The effects of RLX on the heart were discovered in 1990 by Osheroff et al., see Osheroff PL et al., Proc. Natl. Acad. Sci. USA; 1992.89: 2384-2388; and U.S. Pat. No. 5,166,191.
They described the binding of RLX to heart atria and an increase of the rhythm and contractions of the in vitro isolated atria. From these experiments they hypothesized a possible role of RLX in dysfunctions of heart rhythm and in diseases concerning heart contraction, such as congestive heart failure.
Some observations have been done on circulation. It has been noted that the Raynaud's lesions completely disappear during early pregnancy. Early clinical studies made by Casten and Allon in 1958 and 1960 with ovine preparation of RLX of poor purity and uncertain biological activity have shown that it was beneficial in healing Raynaud's lesions arising from obliterative peripheral arterial diseases but the treatment involved use of RLX in combination with small amounts of exogenous estrogen (see Casten G. G. et al., Angiology 11, 408, 1960).
In 1986 it has been reported that local application of porcine RLX to mesocaecum of male rats produces dilation of venulae and antagonizes the vasoconstrictive effects of norepinephrine and promethazine (see: Bigazzi M et al., Acta Endocrinol. 112-296, 1986).
In 1989 Massicotte et al. reported that a two days infusion of rat RLX blunted the vasoconstrictive effects of norepinephrine and vasopressin on mesenteric artery of spontaneously hypertensive rats (see: Massicotte et al.: Proc. Soc. Exp. Biol. Med.:190, 254, 1989).
However, the physiological significance of these observations remained obscure and up to now it was not known whether or not RLX influences the circulatory system.
No effects of RLX have been reported so far on the hemostasis and blood composition.